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Cancer Caused by Diesel Fuel Exhaust Emissions
Published in Ozcan Konur, Petrodiesel Fuels, 2021
Aoki et al. (2001) study the accelerated DNA adduct formation in the lung of the ‘nuclear factor erythroid 2–related factor 2’ (Nrf2) knockout mouse exposed to DE in a paper with 231 citations. They hypothesized that the Nrf2 gene knockout mouse might serve as an excellent model system for analyzing DE toxicity. They examined lungs from Nrf2(−/−) and Nrf2(+/−) mice for the production of xenobiotic–DNA adducts after exposure to DE (3 mg/m3 suspended particulate matter) for four weeks. They found that whereas the ‘relative adduct levels’ (RAL) were significantly increased in the lungs of both Nrf2(+/−) and Nrf2(−/−) mice upon exposure to DE, the increase of RAL in the lungs of Nrf2(−/−) mice exposed to DE were approximately 2.3-fold higher than that of Nrf2(+/−) mice exposed to DE. In contrast, cytochrome P4501A1 mRNA levels in the Nrf2(−/−) mouse lungs were similar to those in the Nrf2(+/−) mouse lungs even after exposure to DE, suggesting that suppressed activity of phase II drug-metabolizing enzymes is important in giving rise to the increased level of DNA adducts in the Nrf2-null mutant mouse subjected to DE. Importantly, they observed severe hyperplasia and accumulation of the oxidative DNA adduct ‘8-hydroxydeoxyguanosine’ (8-OHdG) in the bronchial epidermis of Nrf2(−/−) mice following DE exposure. They showed the increased susceptibility of the Nrf2 germ line mutant mouse to DE exposure and conclude that the Nrf2 gene knockout mouse may represent a valuable model for the assessment of respiratory DE toxicity.
Evaluation of the Potential Oncogenicity of Radiofrequency Fields in Experimental Animal Models
Published in Ben Greenebaum, Frank Barnes, Biological and Medical Aspects of Electromagnetic Fields, 2018
Although one positive result was reported in lymphoma studies in the Eμ-pim-1 transgenic mouse [40], the results of two subsequent studies in the same animal model using apparently superior designs were both negative [41,42]. Three studies in the AKR mouse leukemia/lymphoma model were negative [45–47], as were four studies in the C3H mouse mammary tumor model [49–52] and one study in the heterozygous Ptc1+/− knockout mouse brain cancer model [44]. Because the only reported positive finding in a tumor-prone mouse model was not replicated in two later studies, these data are interpreted as providing no evidence that RFR is carcinogenic in tumor-prone mouse models.
Preclinical Models
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Irene Cuadrado, Jesús Egido, Jose Luis Zamorano, Carlos Zaragoza
Targeted disruption of selected genes is a very powerful tool in therapy research on specific types of cancer as it provides with substantial information about the signaling pathways in which the gene or genes of interest participate as tumor suppressor or tumor formation genes. However, conventional knockout mouse models have sometimes significant limitations based on the pleiotropic effects of the targeted gene of interest. Such is the case of genes that lead to embryonic or infant lethality, or infertility. Breast cancer BRCA genes are a clear example, since single knockout mice die before birth or adulthood (Evers and Jonkers 2006).
Ex vivo study correlating the stiffness of the ovine patellar tendon to age and weight
Published in International Biomechanics, 2022
Françoise Kayser, Edoardo Bori, Sophie Fourny, Fanny Hontoir, Peter Clegg, Alexandra Dugdale, Bernardo Innocenti, Jean-Michel Vandeweerd
Proteoglycans also are involved in viscoelastic changes in aged tendons. Decorin is the most abundant proteoglycan in the small leucine-rich proteoglycan family (SLRP) in tendons. Decorin regulates the assembly of collagen I which is the primary structural unit and transmits mechanical force (Xu et al. 2018). The absence of decorin leads to an abnormal collagen fibrillogenesis, decreased tendon strength and stiffness (Danielson et al. 1997). Decorin and biglycan are essential regulators of collagen fibril and matrix assembly and provide overlapping functions rather than single deficiency-related abnormalities. A study in a both decorin and biglycan gene expression knockout mouse model showed changes in structural properties as a shift to larger diameter fibrils with increased heterogeneity, and altered mechanical properties as decreased stiffness (Robinson et al. 2017). A study carried out on old rats found decreased proteoglycan 4 and elastin mRNA expression in tendons was responsible for the increased tendon stiffness observed with ageing through reduced gliding properties of fascicular sheets (Kostrominova and Brooks 2013).